1. Field of the Invention
The present invention relates to a process for separating .gamma.-globulin aggregate for preparing .gamma.-globulin medicine which does not contains .gamma.-globulin aggregate. More particularly, it relates to a process for separating .gamma.-globulin aggregate by an ultrafiltration membrane to obtain a .gamma.-globulin medicine which is not chemically modified so as to be suitable for intravenous administration.
2. Description of the Prior Art
Among immunoglobulin as a component of plasma proteins, .gamma.-globulin medicine comprising IgG as a main component has been used for prevention and therapeutic of various infection diseases, however, the medicine causes severe anaphylactic reaction due to .gamma.-globulin aggregate, and accordingly, it has been limited to intramuscular injection. In view of medical importance of the medicine, it has been proposed to administrate it by the intravenous administration so as to be further effective administration at large dose in immediate effect.
In order to be capable of the intravenous administration of .gamma.-globulin medicine, it is necessary to reduce an anticomplementary activity as a result of the side-effect. It has been confirmed that the anticomplementary activity is resulted by the aggregation of .gamma.-globulin in the separation of .gamma.-globulin monomer. Certain processes for separating the .gamma.-globulin aggregate or reducing the anticomplementary activity are as follows:
(1) Enzymic treatment PA1 (2) Chemical modification PA1 (3) Process for deaggregating the aggregate in .gamma.-globulin medicine
[Vox Sang. 13 71 (1967)] PA2 [Vox Sang. 28 422 (1965)] PA2 [Japanese Unexamined Patent Publication 103723/1973] PA2 [Acta Chemica Scandinavia 22 490 (1968)]
The process (1) for treating immunoglobulin with pepsin to remove the complement-fixing site has disadvantages that the half-life of antibody activity of .gamma.-globulin in blood is remarkably short and the Fc activity can not be expected.
The process (2) has the disadvantage which is different from the natural condition as intact .gamma.-globulin monomer.
The process (3) is the optimum process for obtaining intact .gamma.-globulin monomer. The product, however result in the aggregate in storage to increase the anticomplementary activity.